OVERVIEW: What every practitioner needs to know

Are you sure your patient has bladder exstrophy? What are the typical findings for this disease?

Bladder exstrophy is a rare congenital birth defect that has severe manifestations in the lower urinary tract, bladder, genitalia, abdominal wall, and bony pelvis. This is one of the largest surgically correctable birth defects that occurs in otherwise healthy newborns. Modern surgical and medical advancements have allowed for surgical reconstruction in infancy and childhood that provides continence, preservation of renal function, cosmetic and functional genitalia, and provides for a good quality of life to those afflicted. Herein the essentials of bladder exstrophy are reviewed.

A pinkish red mucosa-lined structure would be visible on the anterior abdomen. This is the bladder template exteriorized on the outside of the abdomen.

A palpably widened pelvis with widely separated pubic bones.

Additionally, an epispadaic phallus would be present in males. This is a failure of the ventral penis to roll into a tube.

The clitoris and female genitalia would be widely separated.

Cloacal Exstrophy

Cloacal exstrophy is a more severe variant of exstrophy involving exstrophy of the hindgut onto the abdomen along with the bladder. With cloacal exstrophy, one would see imperforate anus, spinal anomalies, omphalocele, and exstrophy as part of the spectrum of defects. Cloacal exstrophy, because it involves many organ systems, represents the most severe variant of the exstrophy complex.

Epispadias

Epispadias is the least severe variant of the exstrophy complex. The bladder remains on the inside of the body, but the genitalia are incompletely fused ventrally. In boys, the pubis may be wider than normal and the penis will be opened on the ventral side. This can range from a glanular epispadias (only on the tip of the penis) to more classic epispadias in which the defect goes back to the bladder neck and may involve the child's continence mechanism.

In girls, wider than normal spacing between the genitalia may be present. The urethra will be opened ventrally, and commonly the epispadias will involve the bladder neck in girls and incontinence will be a presenting symptom.

What other disease/condition shares some of these symptoms?

Epispadias

Cloacal exstrophy

Prune belly syndrome

Omphalocele

Gastroschisis

Patent urachus

What caused this disease to develop at this time?

Bladder exstrophy results from an embryologic insult; either the cloacal membrane ruptures prematurely or mesenchymal ingrowth arrests and fails to completely form ventrally. The exact mechanism remains unclear. Bladder exstrophy is reported to occur between 1 /30,000 and 1/50,000 live births. The literature demonstrates a 2:1 male to female ratio. The risk of recurrence of bladder exstrophy in a given family is 1:100, and the incidence of exstrophy is increased with decreased maternal age, higher parity, and white race. Prenatal ultrasonography has become a means of diagnosing the condition in at least 50% of cases.

On prenatal ultrasonography, several findings may assist in the diagnosis of bladder exstrophy in a fetus. These include the following:

Absence of bladder filling

Anterior abdominal wall mass

Low-set umbilicus

Abnormal widening of the iliac crest

Anteriorly displaced scrotum

Small phallic size in a male

In a newborn, the physical examination will be almost all that is needed to confirm the diagnosis of bladder exstrophy. Typical findings on physical examination will be the following:

Low-set umbilicus

The exstrophic bladder is a circular patch of red mucosa freely draining urine

The pubic symphysis is widened with a palpable diastasis

In boys, the urethra is open on the dorsum of the corporal bodies and the corpora themselves are shortened

In girls, the mons pubis is usually absent and the clitoris is typically bifid

What laboratory studies should you request to help confirm the diagnosis? How should you interpret the results?

Would imaging studies be helpful? If so, which ones?

In all cases of newborns with bladder exstrophy, it is recommended that baseline imaging be obtained, including a kidney/ureter/bladder (KUB) radiograph, renal ultrasonogram, and spinal ultrasonogram. A KUB, or plain abdominal film, allows for measurement of the pubic diastasis to assist in planning operative approaches. A renal ultrasonogram allows for evaluation of baseline renal structure, number, and position. Finally, a spinal ultrasonogram in a newborn is easy to obtain and evaluates the child for associated spinal defects, which can be present in up to 6.7% of patients presenting with classic bladder exstrophy.

Advanced imaging such as computed tomography or magnetic resonance imaging of the pelvis are currently investigational studies and primarily for research purposes at this time.

Confirming the diagnosis

If bladder exstrophy is suspected, consultation with a pediatric urologist is recommended. If no pediatric urologist is available, evaluation by an experienced pediatric surgeon or transfer to a tertiary care center or exstrophy center is recommended. Closure of the bladder can be delayed without causing detrimental long-term outcomes. In exstrophy reconstruction, the most critical step is having the primary closure of the bladder succeed. With regard to confirming the diagnosis, evaluation by a specialist can be helpful; however the diagnosis can usually be confirmed by physical examination alone.

If you are able to confirm that the patient has exstrophy, what treatment should be initiated?

Consultation with a pediatric urologist and a pediatric orthopedist should be undertaken. Surgical closure is recommended.

Closure within the first 72 hours-7 days of life can usually be performed without a pelvic osteotomy (cutting of the pelvic bone). This is generally preferred at exstrophy centers.

Delayed closure in children older than 3-7 days should be performed in conjunction with a pediatric orthopedic surgeon who can perform a proper pelvic osteotomy to aid in bladder and pelvis closure.

There are several different methods of surgical closure of the bladder, but all involve placing the bladder back on the inside of the body and closing the bony pelvis and the abdominal wall and fascia.

Consider transferring the patient to a tertiary care facility or an exstrophy center of excellence.

Cover the bladder template with plastic wrap.

Irrigate the surface of the bladder with normal saline at each diaper change and replace the plastic wrap covering.

Tie off the umbilical cord with silk ligatures and remove any plastic cord clamping device as this can gouge and injure the bladder mucosa.

Long-term treatment: It is preferred that primary closure of the bladder be undertaken within the first 72 hours of life, as that generally saves the child from having a pelvic osteotomy. However there are several reasons to delay primary closure. They include the following:

The child needs to be transferred to an exstrophy center.

The bladder is too small or unsuitable for closure.

The bladder is covered by hamartomatous polyps.

In these circumstances, closure can be delayed several weeks up to 6 months of age without significant impact on long-term cosmetic or functional outcome.

Functional and cosmetic genitalia can be successfully reconstructed with surgery.

What causes this disease and how frequent is it?

Exstrophy occurs in 1/30,000-1/50,000 live births. In a family in which one child is born with bladder exstrophy, the risk of recurrence in that given family is 1/100. The incidence of bladder exstrophy is higher with decreased maternal age and increased parity. Exstrophy occurs most commonly in white individuals. With the popularization of assisted reproductive technology, it has been noted that in vitro fertilization increases the incidence of exstrophy. Additionally, in limited reports misoprostol has been implicated as a teratogen potentially causing exstrophy.

How do these pathogens/genes/exposures cause the disease?

This is unknown and is a current topic of research.

Other clinical manifestations that might help with diagnosis and management

Initial management may be altered by the following:

The bladder template is small or covered by hamartomatous polyps.

The presence of gastrointestinal anomalies such as imperforate anus can be seen in up to 1.8% of cases.

The presence of spinal anomalies (up to 6% of cases) can also change the initial management.

What complications might you expect from the disease or treatment of the disease?

Long-term complications from primary closure of bladder exstrophy include renal damage and hydronephrosis, urinary incontinence, and poor genital cosmesis. Renal damage and hydronephrosis can occur if the bladder outlet was strictured or obstructed after closure, of if recurrent febrile urinary tract infections occur, as all children with exstrophy have vesicoureteral reflux that must be corrected later in life.

Incontinence is curable either with bladder neck reconstructive procedures or continent catheterizable stoma. The risk of incontinence increases if a child has a failed closure, a poor bladder template, or a collagen-rich noncompliant bladder from birth. Genital cosmesis is mostly determined by the severity of the defect on genital anatomy. Reconstruction is almost always possible but must be done within the realm that the child's baseline anatomy will provide.

Are additional laboratory studies available; even some that are not widely available?

There are no additional tests available. At select centers, genetic testing and familial inheritance patterns are being investigated.

How can exstrophy be prevented?

There are no known methods to prevent the formation of bladder exstrophy in utero.

What is the Evidence?

Exstrophy is a rare birth defect, with virtually no randomized controlled trials or longitudinal prospective data. Almost all evidence is level 3 and 4 coming from retrospective reviews and expert opinion.

Ongoing controversies regarding etiology, diagnosis, treatment

Surgical techniques and timing of the steps of reconstruction are still debated today; however the diagnosis and need for appropriate surgical management is universally acknowledged. The gold standard repair is the modern staged repair of exstrophy, which consists of closing the bladder at birth, repairing the epispadaic penis between 6 months and 12 months of age, and then performing a continence procedure during later childhood.

Other techniques exist that combine bladder closure and epispadias repair at birth. In experienced centers, these techniques are delivering similar outcomes. New reports in the literature have reported corporal and glanular atrophy or loss after this method of exstrophy repair that is not seen with the staged approach. The technique selected by the surgical team should be a familiar one with good results for that specific surgeon/exstrophy center.